[en] Stenotrophomonas maltophilia is a nosocomial pathogen with an intrinsic broad-spectrum resistance to beta-lactam compounds and other antibacterial agents. It produces two chromosomal beta-lactamases: a clavulanic acid-sensitive class A (L2) and a tetrameric carbapenemase (L1 or BlaS). We screened 40 S. maltophilia multidrug-resistant clinical isolates recovered between 1995 and 1998 in the Varese Hospital (Italy) for the presence of the metallo-beta-lactamase. The isolates were investigated by phenotypic profiling (enzymatic activity and antibiotic resistance pattern) and molecular methods such as PCR and pulsed-field gel electrophoresis (PFGE) to reveal intraspecies diversity. For the tested S. maltophilia strains, we showed that the beta-lactamase production could be induced by the presence of imipenem (50 mug/ml) in the culture media. Addition of 1 mM dipicolinic acid completely inhibited the hydrolysis of imipenem but decreased that nitrocefin in a strain-dependent manner. Full activity of crude extract towards imipenem could be restored by addition of 1 mM ZnCl2. Finally, the gene encoding the carbapenem-hydrolyzing beta-lactamase from S. maltophilia ULA-511 and 39/95, a clinical strain, were isolated and sequenced. These two strains have a different profile of multidrug resistance. The two metallo-beta-lactamases were found to be isologous. The difference of sensitivity of these two strains was associated to the level of production of the metallo-beta-lactamase.
Alonso A., Martinez J.L. (1997) Multiple antibiotic resistance in Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 41:1140-1142.
Avison M.B., Higgins C.S., Von Heldreich C.J., Bennet P.M., Walsh T.R. (2001) Plasmid location and molecular heterogeneity of the L1 and L2 beta-lactamase genes of Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 45:413-419.
Bellais S., Aubert D., Naas T., Nordmann P. (2000) Molecular and biochemical heterogeneity of class B carbapenem-hydrolyzing bacta-lactamases in Chryseobacterium meningosepticum. Antimicrob. Agents Chemother. 44:1878-1886.
Benson K.K., Raddatz J.K., Rotschafer J.C. (1996) Stenotrophomonas maltophilia: A clinical perspective. J. Infect. Dis. Pharmacother. 2:1-14.
Berg G., Roskot N., Smalla K. (1999) Genotypic and phenotypic relationships between clinical and environmental isolates of Stenotrophomonas maltophilia. J. Clin. Microbiol. 37:3594-3600.
Bush K. (1998) Metallo-β-lactamase: A class apart. Clinic. Infect. Dis. 27:S48-S53.
Cooke P., Heritage J., Kerr K., Hawkey P.M., Newton K.E. (1996) Different effects of zinc ions on in vitro susceptibilities of Stenotrophomonas maltophilia to imipenem and meropenem. Antimicrob. Agents Chemother. 40:2909-2010.
Croize J., Rouhan D., Le Noc P. (1987) Identification des bacilles à Gram négatif aérobies et aéro-anaérobies non exigeants par le système ATB 32 GN. Ann. Biol. Clin. 45:74-77.
Denton M., Todd N.J., Kerr K.G., Hawkey P.M., Littlewood J.M. (1998) Molecular epidemiology of Stenotrophomonas maltophilia isolated from clinical specimens from patients with cystic fibrosis and associated environmental samples. J. Clin. Microbiol. 36:1953-1958.
Denton M., Keer V., Hawkey P.M. (1999) Correlation between genotype and β-lactamases of clinical and environmental strains of Stenotrophomonas maltophilia. J. Antimicrob. Chemother. 43:555-558.
Dufresne J., Vézina G., Levesque R.C. (1988) Cloning and Expression of the imipenem-hydrolyzing β-lactamase operon from Pseudomonas maltophilia in Escherichia coli. Antimicrob. Agents Chemother. 32:819-826.
Felici A., Amicosante G., Oratore A., Strom R., Ledent P., Joris B., Fanuael L., Frère J.M. (1993) An overview of the kinetic parameters of class B β-lactamases. Biochem. J. 291:151-155.
Galleni M., Lamotte-Brasseur J., Rossolini G.M., Spencer J., Dideberg O., Frère J.M. (2001) A standard numbering scheme for class B β-lactamases. Antimicrob. Agents Chemother. 45:660-663.
Garrison M.W., Anderson D.E., Campbell D.M., Carroll K.C., Malone C.L., Anderson R.J., Hollis J.D., Pfaller M.A. (1996) Stenotrophomonas maltophilia: Emergence of multidrug-resistant strains during therapy and in an in vitro pharmacodynamic chamber model. Antimicrob. Agents Chemother. 40:2859-2864.
Howe R.A., Wilson M.P., Walsh T.R., Millar M.R. (1997) Susceptibility testing of Stenotrophomonas maltophilia to carbapenems. J. Antimicrob. Chemother. 40:13-17.
Jorgensen J.H., Ferraro M.J., McElmeel M.L., Spargo J., Swenson J.M., Tenover F.C. (1994) Detection of penicillin and extended-spectrum cephalosporin resistance among Streptococcus pneumoniae clinical isolates by use of the E Test. J. Clin. Microbiol. 32:159-163.
Julve R., Rovira E., Belda A., Prat J., Escoms R., Albert A., Gonzalvo F. (1998) Clinical manifestations of Stenotrophomonas (Xanthomonas) maltophilia infection. An. Med. Interna 15:476-480.
Lecso-Bornet M., Bergogne-Bérénzin E. (1997) Susceptibility of 100 strains of Stenotrophomonas maltophilia to three β-lactams and five β-lactam-β-lactamase inhibitor combinations. J. Antimicrob. Chemother. 40:717-720.
Marty N. (1997) Epidemiological typing of Stenotrophomonas maltophilia. J. Hosp. Infect. 36:261-266.
Monget D., Freney J., Boeufgras J.-M., Desmonceaux M., Guicherd M., Ponchon S. (1985) Nouveaux systèmes d' identification des bacilles à Gram négatif utilisant des tests d'assimilation: API 20 NE et ATB 32 GN. Innov. Techn. Biol. Médecine 6:228-235.
Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 3rd edition. Approvated Standard, M7-A3 1993, 13(25).
Payne D.J., Cramp R., Batson J.H., Neal J., Knowles D. (1994) Rapid identification of metallo- and serine β-lactamases. Antimicrob. Agents Chemother. 38:991-996.
Rasmussen B., Bush K. (1997) Carbapenem-hydrolysing β-lactamases. Antimicrob. Agents Chemother. 41:223-232.
Saino Y., Kobayashi F., Inoue M., Mitsuhashi S. (1982) Purification and properties of inducible penicillin β-lactamase isolated from Pseudomonas maltophilia. Antimicrob. Agents Chemother. 22:564-570.
Saino Y., Inoue M., Mitsuhashi S. (1984) Purification and properties of an inducible cephalosporinase from Pseudomonas maltophilia GN12873. Antimicrob. Agents Chemother. 25:362-365.
Sambrook J., Fritsch E.F., Maniatis T. Molecular cloning: a laboratory manual, 2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; 1989.
Sanchagrin F., Dufresne J., Levesque R.C. (1998) Molecular heterogeneity of the L-1 metallo-β-lactamase family from Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 42:1245-1248.
Sanyal S.C., Mokaddas E.M. (1999) The increase in carbapenem use and emergence of Stenotrophomonas maltophilia as an important nosocomial pathogen. J. Chemother. 11:28-33.
Schmitz F.-J., Sadurski R., Verhoef J., Milatovic D., Fluit A.C. (2000) Typing of 154 clinical isolates of Stenotrophomonas maltophilia by pulsed-field gel electrophoresis and determination of the in vitro susceptibilities of these strains to 28 antibiotics. J. Antimicrob. Chemother. 45:921-924.
Senda K., Arakawa Y., Ichiyama S., Nakashima K., Ito H., Ohsuka S., Shimokata K., Kato N., Ohta M. (1996) PCR detection of metallo-β-lactamase gene (blaIMP) in gram-negative rods resistant to broad-spectrum β-lactams. J. Clin. Microbiol. 34:2909-2913.
Tenover F.C., Arbeit R.D., Goering G.V., Mickelsen P.A., Murray B.E., Persing D.H., Swaminathan B. (1995) Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: Criteria for bacterial strain typing. J. Clin. Microbiol. 33:2233-2239.
Ullah J.H., Walsh T.R., Taylor I.A., Emery D.C., Verma C.S., Gamblin S.J., Spencer J. (1998) The crystal structure of the L1 metallo-β-lactamase from Stenotrophomonas maltophilia at 1.7 Å resolution. J. Mol. Biol. 284:125-136.
VanCouwenberghe C.J., Cohen S.H., Tang Y.J., Gumerlock P.H., Silva J. (1995) Genomic fingerprinting of epidemic strains of Stenotrophomonas maltophilia (formerly Xanthomonas maltophilia) by arbitrarily primed PCR. J. Clin. Microbiol. 33:1289-1291.
Walsh T.R., Hall L., Assinder S.J., Nichols W.W., Cartwright S.J., MacGowan A.P., Bennett P.M. (1994) Sequence analysis of the L1 metallo-β-lactamase from Xanthomonas maltophilia. Biochim. Biophys. Acta 1218:199-201.
Walsh T.R., Payne D.J., Neville T., Tolson D., MacGowan A.P., Bennett P.M. (1997) Sequence analysis and kinetics of the cloned L2 serine-lactamase from Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 41:1460-1462.
Zhang L., Li X.Z., Poole K. (2000) Multiple antibiotic resistance in Stenotrophomonas maltophilia: Involvement of a multidrug efflux system. Antimicrob. Agents Chemother. 44:287-293.
